Three years ago, Brown University researchers discovered new eye cells – indeed a parallel visual system. Now, in a report in Nature, they explain how these exotic cells harness light energy to do their chief job: setting the body’s master circadian clock.

PROVIDENCE, RI – A Brown University team has found
that a protein called melanopsin plays a key role in the inner workings of
mysterious, spidery cells in the eye called intrinsically photosensitive retinal
ganglion cells, or ipRGCs.

Melanopsin, they found, absorbs light and triggers a biochemical
cascade that allows the cells to signal the brain about brightness. Through
these signals, ipRGCs synchronize the body’s daily rhythms to the rising
and setting of the sun. This circadian rhythm controls alertness, sleep, hormone
production, body temperature and organ function.

Visual clues to daily rhythms
Intrinsically photosensitive retinal ganglion cells – ipRGCs, right – were discovered in 2002. New research shows that the protein melanopsin enables ipRGCs to do their job of setting the body’s master circadian clock. It may be an extremely ancient system in terms of evolution, researchers say.

Brown researchers, led by neuroscientist David Berson, announced
the discovery of ipRGCs in 2002. Their work was astonishing: Rods and cones aren’t the only light-sensitive eye cells.

Like rods and cones, ipRGCs turn light energy into electrical
signals. But while rods and cones aid sight by detecting objects, colors and
movement, ipRGCs gauge overall light intensity. Numbering only about 1,000 to
2,000 out of millions of eyes cells, ipRGCs are different in another way: They
have a direct link to brain, sending a message to the tiny region that controls
the body clock about how light or dark the environment is. The cells are also
responsible for narrowing the pupil of the eye.

“It’s a general brightness detection system in the
eye,” said Berson, the Sidney A. Fox and Dorothea Doctors Fox Professor of
Ophthalmology and Visual Sciences. “What we’ve done now is provide
more details about how this system works.”

The research, published in the current issue of Nature,
provides the first evidence that melanopsin is a functional sensory
photopigment. In other words, this protein absorbs light and sets off a chain of
chemical reactions in a cell that triggers an electrical response. The study
also showed that melanopsin plays this role in ganglion-cell photoreceptors,
helping them send a powerful signal to the brain that it is day or night.

The team made the discovery by inserting melanopsin into cells
taken from the kidneys and grown in culture. These cells, which are not normally
sensitive to light, were transformed into photoreceptors when flooded with
melanopsin. In fact, the kidney cells responded to light almost exactly the way
ipRGCs do, confirming that melanopsin is the photopigment for ganglion-cell
photoreceptors.

“This resolves a key question about the function of these
cells,” Berson said. “And so little is known about them, anything we
learn is important.”

Berson and his team made another intriguing finding: The
biochemical cascade sparked by melanopsin is closer to that of eye cells in
invertebrates like fruit flies and squid than in spined animals such as mice,
monkeys or humans.

“The results may well tell us that this is an extremely
ancient system in terms of evolution,” Berson said. “We may have a
bit of the invertebrate in our eyes.”

The research team from Brown included lead author and
post-doctoral research associate Xudong Qiu and post-doctoral research associate
Kwoon Wong, both in the Department of Neuroscience, as well as graduate students
Stephanie Carlson and Vanitha Krishna in the Neuroscience Graduate Program. Tida
Kumbalasiri and Ignacio Provencio from the Uniformed Services University of the
Health Sciences also contributed to the research.